The present invention relates to novel tricyclic compounds and to drug compositions containing such tricyclic compounds.
In the past, it was accepted that xcex2-adrenaline receptors are classified into two groups xcex21 and xcex22, wherein the stimulation by xcex21 induces an increase in the cardiac rate and the stimulation by xcex22 brings about relaxation in the smooth muscle tissue and lowering of blood pressure. Arch et al discovered a compound which exhibits scarce activities to xcex21 and xcex22 but emphasizes lipolysis of fatty cells, wherefrom they have made clear the existence of a third receptor [Nature, 309, 163-165 (1984)]. Afterwards, the primary structure thereof was clarified [Emorine et al: Science, Vol. 245, 1118-1121 (1989)] and the receptor was named as xcex23.
Recently, it has been shown that compounds exhibiting a xcex23-activity are useful as a drug for preventive treatment of diabetes, obesity, hyperlipemia, digestive diseases and depression [Int. J. Obesity 8 (suppl. 1), 93-102 (1984); Nature, 309, 163-165(1984); U.S. Pat. No. 5,120,766; Brit. J. Pharmacol., 103, 1351-1356 (1991); Eur. J. Pharmacol., 219, 193-201 (1992)].
Various compounds with correlation to xcex23 have been reported in the literatures, for example, a compound (BRL 37344) having the following-molecular structure A 
as disclosed in EP 023 385 and in Drugs of the Future, Vol. 16. 797-800 (1991); a compound (CL316, 243) having the following molecular structure 
as disclosed in EP 0 455 006 and J. Med. Chem. Vol. 35, 3081-3084 (1992); a compound having the following molecular structure 
as disclosed in WO9429290; and a compound having the following molecular structure 
as disclosed in EP 0 659 737 in Example 1 thereof. All these compounds have molecular structures different clearly from that of the compound according to the present invention.
There vias known a compound exhibiting a function for increasing the myocardial contraction strength and for antagonizing obesity represented by the following structural formula 
as disclosed in EP 171 702, which is distinguished from the compound according to the present invention in that it has a strong pharmacological activity onto the heart and has a molecular structure quite different from that of the compound according to the present invention.
Further, a compound exhibiting an xcex1, xcex2-blocking activity, namely, a function of lowering the blood pressure, represented by the following structural formula 
is disclosed in Japanese Patent Kokais Sho 55-53262 and Sho 58-41860 and a compound exhibiting a vasodilatoric function represented by the following structural formula 
is disclosed in DE 2 651 572. They are different from the compound according to the present invention in the molecular structure and in function.
There is a demand for a novel and effective medicament or pharmaceutic composition which can be used for therapuetic treatment and preventive treatment of diseases correlating to xcex23, such as diabetes, obesity and hyperlipemia.
The inventors in sound research responding to the existing demand, by synthesizing various compounds and examining their functions reached the discovery that novel tricyclic compounds represented by the general formula (I) given below had xcex23-activities with functions for lowering blood sugar value and for lipolysis, which has led to the completion of the present invention.
Thus, the present invention consists in a compound represented by the general formula (I) or a salt thereof: 
in which R represents hydrogen atom or methyl, R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl, R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro. wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being a lower alkyl, benzyl or NR4R4xe2x80x2 and R6xe2x80x2 being hydrogen atom or lower alkyl, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl, R6 represents hydrogen atom or lower alkyl, X stands for a secondary nitrogen atom, oxygen atom, sulfur atom or methylene and, in case X is secondary nitrogen atom, oxygen atom or sulfur atom, R9 stands for hydrogen atom and either one of R7 and R8 is hydrogen atom and the other one is hydrogen atom, amino, acetylamino or hydroxy, or, in case X is methylene, both R7 and R8 are hydrogen atom and R9 stands for hydrogen atom, amino, acetylamino or hydroxy, *1 indicates an asymmetric carbon atom and *2 indicates that the carbon atom is asymmetric provided that R6 is lower alkyl.
According to the present invention, there may be exemplified for the halogen atom fluorine atom, chlorine atom, bromine atom or iodine atom, among them, fluorine atom and chlorine atom are preferred. In the context of the present invention, xe2x80x9clower alkylxe2x80x9d means a straight or branched chain saturated hydrocarbon having 1-4 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl and t-butyl.
In the formula (I), R may preferably be hydrogen atom, while R may favorably be also methyl for reason of providing more higher selectivity.
R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl. A preferred example of the compound represented by the general formula (I) is one in which R1 denotes hydrogen atom. Also preferred example of the compound represented by the general formula (I) is one in which R1 denotes amino or hydroxymethyl group. A further preferred example of the compound represented by the general formula (I) is one in which R1 denotes halogen atom or hydroxyl or benzyloxy group.
R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro. A preferred example of the compound represented by the general formula (I) is one in which R2 is hydrogen atom. Also preferred example of the compound represented by the general formula (I) is one in which R2 is hydroxymethyl or nitro group. A further preferred example of the compound represented by the general formula (I) is one in which R2 stands for NHR3 or SO2NR4Rxe2x80x2. R3 in the group NHR3 may be hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, wherein preference is given especially to NHR3 which is NH2, NHMe, NHSO2R5 and NHCONHR6xe2x80x2, among which NHSO2R5 is more preferable. In the group NHSO2xe2x80x2R5, R5 stands for lower alkyl, benzyl or NR4R4xe2x80x2, R4 and R4xe2x80x2 may either be identical with or different from each other and may stand each for hydrogen atom, lower alkyl or benzyl, wherein either one of R4 and R4xe2x80x2 is preferably hydrogen.
Concrete examples of NR4R4xe2x80x2 include amino, methylamino, ethylamino, propylamino, benzylamino, dimethylamino, diethylamino, dipropylamino, methylethylamino, methylpropylamino and methylbenzylamino, among which preference is given to methylamino and dimethylamino. Therefore, preferred concrete examples of NHSO2R5 include NHSO2Me, NHSO2Et, NHSO2CH2Ph, NHSO2NH2, NHSO2NHMe, NHSO2NHEt, NHSO2NMe2, NHSO2NEt2, NHSO2NMeEt and NHSO2NMeCH2Ph. R6xe2x80x2 in the group NHCONHR6xe2x80x2 is hydrogen atom or lower alkyl. Concrete examples of NHCONHR6xe2x80x2 include NHCONH2. NHCONHMe, NHCONHEt and NHCONHPr. Concerning the group SONR4R4xe2x80x2 for the group R2, the groups R4 and R4xe2x80x2 have the same meanings as given above and may either be identical with or different from each other and may stand each for hydrogen atom, lower alkyl or benzyl, wherein it is preferable that either one of R4 and R4xe2x80x2 is hydrogen atom. Therefore, concrete examples of the group SO2NR4R4xe2x80x2 include SO2NH2, SO2NHMe, SO2NHEt, SO2NMe2, SO2NEt2, SO2NHCH2Ph and SO2NMeCH2Ph.
R6 represents hydrogen atom or lower alkyl. Preferred examples include hydrogen atom. methyl and ethyl. Here, preference is given to the case where it stands for hydrogen atom.
X stands for secondary nitrogen atom, oxygen atom, sulfur atom or methylene. A preferred example of the compound is one in which X is secondary nitrogen atom, namely, the tricyclic skeleton is constituted of carbazole group. Here, the groups R7, R8 and R9 have the meanings as given previously.
The symbol *1 in the general formula (I) indicates an asymmetric carbon atom and, in case R6 is lower alkyl, the symbol *2 also indicates an asymmetric carbon atom. In this case, the compound of the general formula (I) may be present in four isomers, namely, (R,R), (R,S), (S,S) and (S,R) represented by the sequence of (*1, *2). In case R6 is hydrogen atom, two isomers are possible. The present invention encompasses not only each optically pure isomer, but also mixtures of two voluntarily selected isomer, of three voluntarily selected isomers and of all four isomers. From the point of view of development of the pharmacological activity, an asymmetric carbon atom (*1) in the ethanolamino chain may preferably have an absolute configuration (R). Concerning the asymmetric carbon atom (*1) for N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide, especially preferred examples are R-hydroxy compounds.
For the compound according to the present invention, there are very favorable groups of combinations of the substituent groups. In the following, the symbols R6, X, R7, R8, R9, *1 and *2 for the general formula (I) have the meanings as defined above, so long as no special mention is made.
When R2 in the general formula (I) for the compound according to the present invention represents hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, it is preferable that the group R1 is in the 4- or 5-position, wherein preference is given to the case where R1 is in 4-position. When R2 is hydrogen atom, it is more preferable that R1 is in the 2-position.
Preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for hydrogen atom, a halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl and R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5. formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2 and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for hydrogen atom, fluorine atom, chlorine atom, hydroxy or benzyloxy and R2 stands for hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2 and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl, with R5 being lower alkyl, benzyl or dimethylamino and R6xe2x80x2 being the same as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for hydrogen atom, halogen atom, hydroxy or benzyloxy and R2 stands for hydroxymethyl, NHR3, SO2N4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl. SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2 and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, a lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for hydrogen atom, fluorine atom, chlorine atom, hydroxy or benzyloxy and R2 stands for hydroxymethyl, NHR3, SO2N4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2 and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl, benzyl, with R5 being lower alkyl, benzyl or dimethylamino and R6xe2x80x2 being the same as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR and R1 represent each hydrogen and R2 stands for hydroxymethyl, NHR3 or SO2N4R4xe2x80x2, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2 with R5 being lower alkyl, benzyl or NR4R4xe2x80x2 and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl, and R6xe2x80x2 being the same as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR and R1 represent each hydrogen atom and R2 stands for hydroxymethyl, NHR3 or SO2NR4R4xe2x80x2, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2 and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl, with R5 being lower alkyl, benzyl or dimethylamino and R6xe2x80x2 being the same as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for halogen atom or hydroxy and R2 stands for NHSO2R5 or SO2NR4R4xe2x80x2, wherein R5 is lower alkyl, benzyl or NR4R4xe2x80x2 and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzylxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for fluorine atom, chlorine atom or hydroxy and R2 stands for NHSO2R5 or SO2NR4R4xe2x80x2, wherein either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl and R5 is lower alkyl, benzyl or dimethylaminoxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR and R2 represent each hydrogen atom and R1 stands for hydrogen atom, halogen atom or hydroxyxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR and R2 represent each hydrogen atom and R1 stands for hydrogen atom, fluorine atom, chlorine atom or hydroxyxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents hydrogen atom, R1 stands for hydrogen atom, halogen atom, hydroxy, amino or hydroxymethyl and R2 stands for NHR3 or SO2NR4R4xe2x80x2, wherein R3 is SO2R5, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzylxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl and R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, fluorine atom, chlorine atom, hydroxy or benzyloxy and R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2, and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, halogen atom, hydroxy or benzyloxy and R2 stands for hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, fluorine atom, choline atom, hydroxy or benzyloxy and R2 stands for hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or dimethylamino, and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom and R2 stands for hydroxymethyl, NHR3, SO2NR4R4xe2x80x2, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom and R2 stands for hydroxymethyl, NHR3 or SO2NR4R4xe2x80x2, wherein R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or dimethylamino, and either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl and R6xe2x80x2 has the meaning as given abovexe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for halogen atom or hydroxy and R2 stands for NHSO2R5 or SO2NR4R4xe2x80x2 wherein R5 is lower alkyl, benzyl or NR4 R4xe2x80x2, and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzylxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for fluorine atom, chlorine atom or hydroxy and R2 stands for NHSO2R5 or SO2NR4R4xe2x80x2, wherein either one of R4 and R4xe2x80x2 is hydrogen atom and the other one is hydrogen atom, lower alkyl or benzyl and R5 is lower alkyl, benzyl or dimethylaminoxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, a halogen atom or hydroxy and R2 stands for hydrogen atomxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, fluorine atom, chlorine atom or hydroxy and R2 stands for hydrogen atomxe2x80x9d.
Also preferred examples of the compound represented by the general formula (I) or the salt thereof according to the present invention are those in which the combination of the substituent groups in the general formula (I) is such that xe2x80x9cR represents methyl, R1 stands for hydrogen atom, halogen atom, hydroxy, amino or hydroxymethyl and R2 stands for NHR3 or SO2NR4R4xe2x80x2, wherein R3 is SO2R5, with R5 being lower alkyl, benzyl or NR4 R4 , and R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alkyl or benzylxe2x80x9d.
Concrete examples of the compound represented by the general formula (I) according to the present invention include
(R)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
(S)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(3-hydroxy-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(3-amino-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(6-amino-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(6-hydroxy-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
(R)-N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
(S)-N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-methyl-3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]benzenesulfonamide,
N-methyl-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxy]benzenesulfonamide,
(R)-N-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
(S)-N-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]1-hydroxyethyl]2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2 (dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-(benzyloxy)phenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]methanesulfonamide,
N-[3-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-[5-[2-[2-(7-acetylaminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(7-aminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[3-[2-[2-(7-acetylaminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-[3-[2-[2-(7-aminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]formamide,
N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]formamide,
N-[3-[2-[[1-(9H-carbazol-2-yloxy)propan-2R-yl]amino]-1-hydroxyethyl]phenyl]methanesulfonamide,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(4-hydroxy-3-nitrophenyl)ethanol,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(3-amino-4-hydroxyphenyl)ethanol.
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-(benzyloxy)phenyl]urea,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]urea,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-(benzyloxy)phenyl]formamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-(benzyloxy)phenyl]-N,N-dimethylsulfamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-[3-(methylamino)-4-(benzyloxy)phenyl]ethanol,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-[3-(methylamino)-4-hydroxyphenyl]ethanol,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-2-propanesulfonamide,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(3-nitrophenyl)ethanol,
Nxe2x80x2-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]-N,N-dimethylsulfamide,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(3-aminophenyl)ethanol,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-[3-(hydroxymethyl)-4-hydroxyphenyl]ethanol,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-3-hydroxyphenyl]methanesulfonamide,
N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[3-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-4-hydroxyphenyl]methanesulfonamide,
(R)-Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
(S)-Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
N-[3-[2-[2-(6-acetylamino-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
N-[5-[2-[2-(6-acetylamino-9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
(R)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]methanesulfonamide,
(S)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]methanesulfonamide,
(R)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]methanesulfonamide,
(S)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]methanesulfonamide,
N,N-dimethyl-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxy]benzenesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-iodophenyl]methanesulfonamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]-N,N-dimethylsulfamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]-N,N-dimethylsulfamide,
(R)-N-methyl-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxy]benzenesulfonamide,
(R)-N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenyl]methanesulfonamide,
(R)-N-[3-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
Nxe2x80x2-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
(R)-Nxe2x80x2-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
(S)-Nxe2x80x2-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
N-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]methanesulfonamide,
N-[5-[2-[2-(dibenzofuran-3-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]methanesulfonamide,
N-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
Nxe2x80x2-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
N-[3-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]phenyl]methanesulfonamide,
(R)-N-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(dibezothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-fluorophenyl]methanesulfonamide,
N-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-hydroxyethyl]-2-chlorophenyl]methanesulfonamide,
N-[5-[2-[2-(7-aminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide,
Nxe2x80x2-[5-[2-[2-(7-acetylaminofluoren-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N,N-dimethylsulfamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-aminophenyl]-N-benzyl-N-methylsulfamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-aminophenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxymethylphenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-bromophenyl]methanesulfonamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenyl]-N-benzyl-N-methylsulfamide,
Nxe2x80x2-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-hydroxyethyl]-2-hydroxyphenytl]-N,N-diethylsulfamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-methoxyethyl]-2-aminophenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-methoxyethyl]-2-hydroxyphenyl]methanesulfonamide and
N-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-methoxyethyl]-2-hydroxyphenyl]methanesulfonamide.
The followings are concrete examples of the compound in which both R1 and R2 are hydrogen.
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(4-hydroxyphenyl)ethanol,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(2-fluorophenyl)ethanol,
2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-(2-hydroxyphenyl)ethanol,
(R,R)-2-[N-[1-(9H-carbazol-2-yloxy)propan-2-yl]amino]-1-phenyl]ethanol,
[2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
(R)-[2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
(S)-[2-[N-[2-(9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
[2-[N-[2-(3-acetylamino-9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
[2-[N-[2-(3-amino-9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
[2-[N-[2-(3-hydroxy-9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol
[2-[N-[2-(6-amino-9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
[2-[N-[2-(6-acetylamino-9H-carbazol-2-yloxy)ethyl]amino]-1-phenyl]ethanol,
[2-[N-[1-(9H-carbazol-2-yloxy)propan-2-yl]amino]-1-phenyl]ethanol and
[2-[N-[2-(dibenzofuran-3-yloxy)ethyl]amino]-1-phenyl]ethanol.
Examples of the compounds in which R stands for methyl include the followings.
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-methoxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(dibenzothiophen-3-yloxy)ethylamino]-1-methoxyethyl]-2-hydroxyphenyl]methanesulfonamide,
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-methoxyethyl]-2-aminophenyl]methanesulfonamide and
N-[5-[2-[2-(9H-carbazol-2-yloxy)ethylamino]-1-methoxyethyl]-2-chlorophenyl]methanesulfonamide.
The compound represented by the general formula (I) can be produced, for example, by the following method.
 less than  less than Production Process A greater than  greater than 
A compound represented by the general formula (II) 
[in which R1xe2x80x2 represents hydrogen atom, halogen atom, a protected hydroxyl group protected by a protecting group A, a protected amino group protected by acetyl group or a protected hydroxymethyl group protected by acetyl group, R2xe2x80x2 stands for hydrogen atom, for a protected hydroxymethyl group in which the hydroxyl group is protected by a protecting group Axe2x80x2xe2x80x3, for NHR3xe2x80x2, for SO2NR4R4xe2x80x2 or for nitro, wherein R3xe2x80x2 represents a protecting group for the amino group, methyl, SO2R5, formyl or CONHR6xe2x80x2, with R5 being lower alkyl, benzyl or NR4R4xe2x80x2 and R6xe2x80x2 being hydrogen atom or lower alkyl, R4 and R4xe2x80x2 may be identical with or different from each other and stand each for hydrogen atom, lower alky or benzyl, R6 denotes hydrogen atom or lower alkyl, Axe2x80x2 represents a protecting group for the hydroxyl group, B is bromine atom or iodine atom and *1 indicates an asymmetric carbon atom] is reacted with a compound represented by the general formula (III) 
[wherein Y represents hydrogen atom, R6 is hydrogen atom or lower alkyl, X is secondary nitrogen atom, oxygen atom, sulfur atom or methylene and, in case X is secondary nitrogen atom, oxygen atom or sulfur atom. R9xe2x80x2 is hydrogen atom and either one of R7xe2x80x2 and R8xe2x80x2 is hydrogen atom and the other one is hydrogen atom, acetylamino or a protected hydroxyl group protected by a protecting group Axe2x80x3, or, in case that X is methylene, both R7xe2x80x2 and R8xe2x80x2 are hydrogen atom and R5xe2x80x2 stands for hydrogen atom, acetylamino or a protected hydroxyl group protected by a protecting group Axe2x80x3, and *2 indicates asymmetric carbon atom, when R6 is lower alkyl], and the protecting groups A (proviso that in case that R1 is benzyloxy and the protecting group A is benzyl, the protecting group A is not deprotected), Axe2x80x2, Axe2x80x3, Axe2x80x3xe2x80x2 and the protecting group for amino group in R3xe2x80x2 (proviso that if is exists), or the protecting acetyl group in R1xe2x80x2 are deprotected to obtain the compound represented by the general formula (I), [wherein R represents hydrogen atom, R1 stands for hydrogen atom, halogen atom, hydroxy, benzyloxy, amino or hydroxymethyl, R2 stands for hydrogen atom, hydroxymethyl, NHR3, SO2NR4R4xe2x80x2 or nitro, proviso that R3 is hydrogen atom, methyl, SO2R5, formyl or CONHR6xe2x80x2, and R5 is lower alkyl, benzyl or NR4R4xe2x80x2 and R4 and R4xe2x80x2 may be identical with or different from each other and are hydrogen atom, lower alkyl or benzyl group. R6xe2x80x2 is represents hydrogen atom or lower alkyl.
As the protecting groups for protecting the hydroxyl groups, there is no special limitation so long as ordinary use is permitted and there may usually be used as a protecting group which can be deprotected easily and selectively, for example, benzyl or t-butyl-dimethylsilyl for the protecting group A, triethylsilyl for the protecting groups Axe2x80x2 and Axe2x80x3xe2x80x2 and methyl or benzyl for the protecting group Axe2x80x3. For introducing a protecting group into the compound to be protected, known practice is employed and, for example, a method is used for protecting the compound by introducing therein benzyl group, in which the compound is reacted with 1.1 molar times benzyl bromide at room temperature in a reaction solvent, such as dimethylformamide, in the presence of potassium carbonate. For protecting the compound by introducing therein triethylsilyl group, the compound is reacted with 1.2-2 molar times silylating agent, such as triethylsilyl chloride, at a temperature in the range of 0 to 30xc2x0 C. in a reaction solvent, such as pyridine, for 1-3 hours.
As the protecting group for protecting the amino group in the substituent R3xe2x80x2, there is no special limitation so long as ordinary use as a protecting group for protecting aniline is permitted and acetyl group may usually be preferred therefor. For practising the acetylation, a reaction with acetic anhydride in a reaction solvent, such as pyridine, may be exemplified.
The coupling reaction of the compound represented by the general formula (II) with the amine represented by the general formula (III) may be realized using 1 to 1,5 moles of the amine of the general formula (III) per 1 mole of the halide of the general formula (II) in a polar solvent, such as dimethylformamide, dimethylacetamide or dimethylsulfoxide, in the presence of a proton capturing agent, for example, an amine, such as triethylamine or diisopropylethylamine, at a temperature in the range from room temperature to 90xc2x0 C., preferably by heating at 60xc2x0 C., for 5-10 hours.
Deprotection of the resulting product may be effected either in succession or simultaneously, while deprotection in a successive order of Axe2x80x3, Axe2x80x2 Axe2x80x3xe2x80x2, the protecting agent for the amino group in R3xe2x80x2 and at last A may be preferred. The deprotection of benzyl group for A and Axe2x80x3 is realized by hydrogenolysis in a solvent, such as methanol, using a catalyst, such as palladium or nickel. In the case where the substituent R1 in the general formula (I) is benzyloxy, there is no need of elimination of benzyl group as the protecting group A. The deprotection of benzyl or methyl as the protecting groups A and Axe2x80x3 may be realized by treating the product with a Lewis acid, such as boron tribromide, in a solvent, such as methylene chloride. The deprotection of acetyl-protected hydroxyl group in the substituent R1xe2x80x2 may be realized by a known procedure of hydrolysis of ester. Concretely, it may be performed in an alcohol using an alkali at room temperature or by heating under reflux of the solvent. The deprotection of triethylsilyl as the protecting group Axe2x80x2 or Axe2x80x3xe2x80x2 may be realized by treating the product by adding thereto acetic acid and 3-5 molar times tetrabutylammonium fluoride in a solvent of tetrahydrofuran at room temperature for 30-5 hours. The deprotection of the protecting group, such as acetyl, for the amino group in R3xe2x80x2 or of the acetyl-protected amino group in R1xe2x80x2 may be realized either by treating the product with hydrochloric acid at room temperature or by heating in a solvent, such as water or methanol, with an alkali.
The compound represented by the general formula (II) can be obtained ba subjecting a compound represented by the following general formula (V), 
in which R1xe2x80x2 and R2xe2x80x2 have the same meanings as given previously, to a reduction in the manner as described below, and replacing the bromide, if the contemplated substituent group B in the general formula (II) is iodine, iodide, followed by protection of the hydroxyl group.
The reduction of the compound represented by the general formula (V) may be attained by using a reducing agent, such as a borane, when the steric configuration (*1) of the hyroxyl group of the compound represented by the general formula (II) is racemic.
In case where either R- or S-optical isomer is to be obtained as to the *1 structure in the general formula (II), the reduction can be attained by having resort to employment of a chiral assistant, such as given by the following general formula (VI). 
Thus, the reduction of the compound represented by the general formula (V) is effected using a borane in the presence of the above-mentioned chiral assistant. The reduction may preferably be performed in a solvent, such as tetrahydrofuran. The preparation of such a chiral assistant and the reaction therewith may be carried out in accordance with the teachings in the literature [E. J. Corey et al, J. Org. Chem., Vol.56, 442, (1991)].
After the reduction of the compound represented by the general formula (V), the bromide thereof is, if necessary, replaced with iodide by, for example, treating the reduced compound with 3-10 times molar amount of an iodizing agent, such as sodium iodide, in a solvent, such as acetone, with heating under reflux for 1-3 hours.
The hydroxyl group of the so-treated product is then protected by the method described previously with a protecting group, such as triethylsilyl, to obtain the compound represented by the formula (II).
The compound represented by the general formula (V) is known and can be synthesized by methods given in literatures, for example, A. A. Larsen et al, J. Med. Chem. 10, 462 (1967); or C. Kaiser et al, J. Med. Chem. 17, 49 (1974).
The compound represented by the general formula (III) can be obtained by reacting a compound represented by the general formula (VII) 
in which Y denotes a protecting group for the amino group, R6 and *2 have the same meanings as those given previously, with a compound represented by the general formula (VIII) 
in which X, R7xe2x80x2, R8xe2x80x2 and R9xe2x80x2 have the same meanings as those given previously. As the protecting group Y for protecting the amino group, there is no special limitation so long as a usual use is permitted and there may be exemplified one Which can usually be deprotected easily, for example, benzyloxycarbonyl, a substituted benzyloxycarbonyl, t-butoxycarbonyl, acetyl or trifluoroacetyl.
The reaction of the compound represented by the general formula (VII) with the compound represented by the general formula (VIII) can be realized, for example, in an organic solvent usually in the presence of a base at a temperature from room temperature to the reflux temperature of the solvent employed. As the solvent, there may be employed, for example, dimethylformamide, dimethylacetamide, acetonitrile, diglym and tetrahydrofuran. As the base, there may be employed, for example, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, pyridine, sodium hydride or sodium methoxide, in an amount of, preferably, 1-10 moles per one mole of the compound of the general formula (VIII).
The compound represented by the general formula (III) can, in particular, if the above reaction does not proceed promptly, also be synthesized in accordance with the process described in Bull. Chem. Soc. Japan, 55, 2504 (1982) or by an improvement thereof. For example, one mole of the alcohol compound is reacted with 2-5 moles of the compound represented by the general formula (VII) in a solvent, such as dimethylformamide or acetonitrile, in the presence of 5-10 moles of 40% potassium fluoride-alumina at a temperature in the range from room temperature to 90xc2x0 C. In the improved process, the above reaction is realized with addition of 0.1-0.5 equivalent of potassium iodide.
Then, the protecting group Y for protecting the amino group is deprotected to obtain the amine compound represented by the general formula (III) wherein Y stands for hydrogen atom. The deprotection may be effected by a usual method, for example, by a hydrogenolysis in a solvent, such as methanol, using a catalyst, such as palladium/carbon black or by treating with hydrogen bromide/acetic acid. If the protecting group Y is acetyl or trifluoroacetyl, the deprotection may be attained by treating with an alkali in a solvent, such as methanol, to obtain the compound represented by the general formula (III) in which Y denotes hydrogen atom.
The compound represented by the general formula (VII) can be synthesized from a commercial product of an amino alcohol having the substituent R6 and a stereo structure of *2 by first protecting the amino group thereof with a protecting group Y and, then, the resulting product is subjected to bromination by a usual method. If there is an easily available aminobromo compound, the contemplated compound can be obtained by merely protecting the amino group by a protecting group Y. For example, a hydrobromide salt of a commercial 2-bromoethylamine may be reacted with benzyloxycarbonyl chloride in a solvent, such as methylene chloride, in the presence of triethylamine under cooling with ice water.
The compound represented by the general formula (III) in which X stands for secondary nitrogen atom, oxygen atom or sulfur atom and that in which X stands for methylene can be produced by the methods given below, respectively.
The compound of the general formula (VIII) in which X is secondary nitrogen atom, oxygen atom or sulfur atom, both R8xe2x80x2 and R9xe2x80x2 are hydrogen atom and R7xe2x80x2 is hydrogen atom, acetylamino or a protected hydroxyl group protected by a protecting group Axe2x80x3 can be produced in a manner as follows:
Thus, starting from a commercial product of 2-hydroxycarbazole and 3-methoxydibenzofuran or 3-hydroxydibenzothiophene which can be synthesized by method given in literature [H. Kudo et al, J. Heterocycl. Chem., 22(1), 215-218 (1985)],the compound represented by the formula (VIII) is obtained. The compound of the general formula (VIII) in which R7xe2x80x2 is a substituent group other than hydrogen atom can be obtained by, for example, in such a manner that the hydroxyl group of a commercial product of 2-hydroxycarbazole is protected by benzylating it, then, nitration is effected to introduce nitro group at the position of the substituent group R7xe2x80x2 and this is reduced into amino group, whereupon this amino group is acetylated or is subjected to diazotization with subsequent conversion into hydroxyl group, followed by protection of the resulting hydroxyl group by a protecting group Axe2x80x3 and subsequent deprotection of the benzyl group to build up the compound of the general formula (VIII).
For the nitration, ordinary methods given in the literatures may be employed, wherein, for example,the benzyl-protected product is subjected to nitrationin acetic acid using an equivalent amount of diluted fuming nitric acid at a temperature of from room temperature to 60xc2x0 C. Reduction of the resulting nitro group may be effected by a usually employed method, for example, by hydrogenation in a solvent, such as methanol, in the presence of a catalyst, such as palladium oxide at room temperature or by using hydrochloric acid with iron powder or in the presence of divalent tin at a temperature in the range from room temperature to the reflux temperature. The resulting amine may be acetylated using acetylchloride in a solvent, such as methylene chloride, at a temperature of from 0xc2x0 C. to room temperature or may be converted into hydroxyl group by first diazotizing it using, for example, sodium nitrite, and, then, subjecting the resulting diazonium salt to a thermal decomposition in an acidic aqueous solution, followed by protection of the resulting hydroxyl group with a protecting group Axe2x80x3 by the technique for protecting hydroxyl group described previously and, finally, deprotecting the benzyl group.
The compound of the general formula (VIII) in which X is secondary nitrogen atom, oxygen atom or sulfur atom, both R7xe2x80x2 and R9xe2x80x2 are hydrogen atom and R8xe2x80x2 is hydrogen atom, acetylamino or a protected hydroxyl group protected by a protecting group Axe2x80x3 can be produced in the manner as follows:
Thus, it can be synthesized starting from a known compound, i.e. 2-acetylcarbazole represented by the general formula (IX) 
in which X is secondary nitrogen atom, oxygen atom or sulfur atom [J. B. Kyziol et al, Tetrahedron, 36, 3017-3019 (1980)], 3-acetyldibenzofuran [M. I. Shevchuk etal, Zh. Obshch. Khim., 40 (8). 1717-1725 (1970)] or 3-acetyldibenzothiophene [Phosphorus. Sulfur Silicon Relat. Elem., 72(1-4). 13-31 (1992); E. Camagine etal, J. Heterocycl. Chem., 6 (4), 517-522 (1969)]. For the compound in which R8xe2x80x2 is a substituent group other than hydrogen atom, it may be processed, for example, by nitrating 2-acetylcarbazole at its position of the substituent group R8xe2x80x2, followed by reduction of the resulting nitro group into amino group, whereupon the amino group is subjected to either acetylation or diazotization with subsequent conversion into hydroxyl group, which is then protected by a protecting group Axe2x80x3 for protecting hydroxyl group.
For example, for producing the compound represented by the general formula (VIII) from the so-obtained acethyl group-containing compound, namely, for converting the acetyl group into hydroxyl group, the acetyl group at the 2-position of carbazole is oxidized by a peracid into acetyloxy which is, then, subjected to hydrolysis. Other process steps than the oxidation of the acetyl group and the hydrolysis may be accomplished in the same manner as in the case of introduction of R7xe2x80x2 described above. The oxidation by a peracid can be realized using, for example, m-chloro-perbenzoic acid and disodium hydrogenphosphate in a solvent, such as methylene chloride, at room temperature and the hydrolysis can be realized by, for example, using sodium hydroxide in a mixed solvent of water/ethanol.
The compound represented by the general formula (VIII) in which X is methylene (fluorene), both R7xe2x80x2 and R8xe2x80x2 are hydrogen atom and R9xe2x80x2 is hydrogen atom or acetylamino is known and a commercial product thereof is available from, for example, the firm Sailor. In the case where R9xe2x80x2 is a protected hydroxyl group protected by a protecting group Axe2x80x3, the compound can be produced by protecting the hydroxyl group of fluorene with benzyl group, de-protecting the acetyl group in the acetylamino group, diazotizing the resulting amino group, converting it into hydroxyl group via a diazonium salt, protecting the resulting hydroxyl group by a protecting group Axe2x80x3 for protecting hydroxyl group and finally de-protecting the benzyl group. These reaction series can be performed by the method described previously.
Alternatively, for producing the compound of the general formula (III) in which either one of R7xe2x80x2, R8xe2x80x2 and R9xe2x80x2, is a protected hydroxyl up protected by a protecting group Axe2x80x2xe2x80x2, methods as given below may be incorporated.
Thus, the compound represented by the general formula (III) in which Y denotes a protecting group for protecting amino group, R7xe2x80x2, R8xe2x80x2 and R9xe2x80x2 denote each acetyl group in accordance with X and R6 and *2 have the same meanings as those given previously is subjected to hydrolysis of the acetylamino group thereof into amino group. The resulting amino group is diazotized and converted into hydroxyl group, which is then protected by a protecting group Axe2x80x3, whereupon the protecting group Y of the amino group is deprotected to obtain the compound represented by the general formula (III) in which Y is hydrogen atom.
As a further alternative method, the compound represented by the general formula (I) in which R is hydrogen atom can be obtained using a compound represented by the general formula (IV) 
in which Yxe2x80x2 is hydrogen atom or a protecting group for amino group and R1xe2x80x2, Axe2x80x2, R6, X, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2, *1 and *2 have the same meanings as those given previously, as an important synthesis intermediate.
For producing the compound represented by the general formula (IV), the compound represented by the general formula (II) in which R2xe2x80x2 is nitro and the compound represented by the general formula (III) in which Y stands for hydrogen atom are brought into coupling reaction and, if necessary, the amino group of the reaction product is protected. The protecting group for the amino group in the substituent group Yxe2x80x2 of the general formula (IV) may be the same as that for the amino group in the substituent group Y explained above and the introduction and elimination thereof may also be effected in the same manner.
For producing the compound represented by the general formula (I) using the compound represented by the general formula (IV) as a synthesis intermediate, the following techniques may be exemplified:
Thus, the compound represented by the general formula (IV) is first reduced, namely, the nitro group thereof is reduced, to obtain a compound represented by the general formula (X) 
in which Yxe2x80x2 is a protecting group for the amino group and R1xe2x80x2, Axe2x80x2, R6, X, R7xe2x80x2, R8xe2x80x2, *1 and *2 have the same meanings as those given previously.
For the above-mentioned reduction, the amino group of the compound of the general formula (IV) may preferably have been protected by the protecting group Yxe2x80x2 and the reduction may be performed by, for example, hydrogenating the compound in a solvent, such as methanol, in the presence of a catalyst, such as palladium oxide, or by using a system employing hydrochloric acid with iron powder or a divalent tin.
Thereafter, the resulting product is subjected to formulation. sulfonation or urearization of amine (aniline) in accordance with the requirement for providing various substituent groups for R3 by, for example, a method described in the literature, C. Kaiser et al, J. Med. Chem., 17. 49 (1974), to convert it into a compound represented by the general formula (XI) 
in which Yxe2x80x2, R1xe2x80x2, Axe2x80x2, R3, R6, X, R7xe2x80x2, Rxe2x80x2, R9xe2x80x2, *1 and *2 have the same meanings as those given previously, whereupon the existing protecting groups among A, Axe2x80x2, Axe2x80x3 and that for the amino group in Yxe2x80x2 are de-protected by the method for deprotection described previously, to produce the compound represented by the general formula (I) in which R is hydrogen atom.
The formylation mentioned above may be effected by, for example, heating the resulting product of the general formula (X) in ethyl formate or by reacting it with a mixture of formic acid/acetic anhydride at a temperature of from cooling with ice water to room temperature. The above mentioned sulfonation may be effected by, for example, reacting the resulting compound of the general formula (X) with a sulfonyl chloride substituted by a group R5 in a solvent, such as pyridine, at a temperature of from cooling with ice water to room temperature. The urearization mentioned above can be attained by. for example, reacting the resulting compound of the general formula (X) with sodium cyanate (NaOCN) at room temperature or under heating at, for example, 60xc2x0 C. in a mixed solvent of water/acetic acid.
Alternatively, there is a method in which a racemic compound is obtained by a brief process step using, in the place of the compound of the general formula (II), the compound represented by the general formula (V) 
in which R1xe2x80x2 and R2xe2x80x2 have the same meanings as given previously.
Thus, the compound represented by the above general formula (V) is reacted with the compound represented by the general formula (III) in which Y is hydrogen atom and the resulting ketoamine compound is, then, reduced, whereupon the protecting groups A, Axe2x80x2, Axe2x80x3 and that for protecting the amino group in the group R3xe2x80x2 are de-protected, with the proviso that the deprotection of the protecting group A is unnecessary for the case where R1 stands for benzyloxy and the protecting group A is benzyl, whereby the compound represented by the general formula (I) in which R is hydrogen atom and R1, R2, R6, X, R7, R8, R9, *1 and *2 have the same meanings as those given previously is obtained.
The reaction of the compound of the general formula (V) with the compound of the general formula (III) can be attained by the method disclosed in the literature. A. A. Larsen et al. J. Med. Chem. 10, 462 (1967), with an improvement in such a manner that the reaction is effected in a polar solvent, such as acetonitrile, dimethylformamide, dimethylacetamide or dimethylsulfoxide, in the presence or absence of an amine as the acid-capturing agent under cooling with ice water or with heating at a temperature up to 60xc2x0 C., followed by reduction of the carbonyl group using a reducing agent, such as sodium borohydride or sodium cyanoborohydride, under cooling with ice water or at room temperature, followed by deprotection of the protecting group. By this reaction, a racemic mixture of *1 is obtained. so that an optical resolution by the method as given afterwards becomes necessary for obtaining each optical active compound.
 less than  less than Production Process B greater than  greater than 
As an alternative production process in which each optical active compound or racemic modification is obtained, a technique using an epoxide may be incorporated.
Thus, the compound represented by the general formula (I) in which R is hydrogen atom and R1, R2, R6, X, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2, *1 and *2 have the same meanings as those given previously can be produced by reacting a compound represented by the general formula (XII), 
in which Rxe2x80x2, R2xe2x80x2 and *1 have the meanings as those given previously, with the compound represented by the general formula (III) in which Y denotes hydrogen atom and X, R6, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2 and *2 have the same meanings as those defined previously, followed by deprotection of the pretecting groups A, Axe2x80x3, Axe2x80x3xe2x80x2, that for protecting the amino group in the substituent R3 and the protecting acetyl group for R1xe2x80x2 by the method described in the paragraph xe2x80x9cProduction Process Axe2x80x9d, with the proviso that the deprotection of the protecting group A is unnecessary when R1 is benzyloxy and the protecting group A is benzyl.
The reaction of the compound represented by the general formula (XII) with the compound represented by the general formula (III) can be carried out in a usual organic solvent, for example, dimethylsulfoxide, a straight chained or cyclic ether, dimethylformamide or dimethylacetamide. While the compound represented by the general formula (XII) and that represented by the general formula (III) are used often in an equimolar proportion, it is preferable to use an excess of the compound represented by the general formula (III) over the compound of the general formula (XII). The reaction is effected at an adequate temperature and, usually, at room temperature or the reflux temperature of the solvent employed. The reaction duration may be selected in accordance with the reaction condition and other factors and, usually, the reaction can be terminated at the point at which the yield becomes maximum.
It was reported that the yield of the reaction can be increased and the reaction duration is reduced by adding to the reaction mixture trimethylsilylacetamide (TMSA) [N,O-bis(trimethylsilylacetamide)], hexamethyldisilazane (HMDS) or bis(trimethylsilyl)urea [Tetrahedron Letters, 27, 2451 (1986)] and this may adequately be incorporated herein.
The compound represented by the general formula (XII) is known and can be synthesized by an ordinary method given in chemical literatures. For example, the general formula (XII) can be produced by oxidizing styrene or a substituted styrene derivative using a peracid, such as m-chloroperbenzoic acid, or by reacting dimethylsulfonium methylideor dimethylsulfoxonium methylide with a substituted benzaldehyde having a substituent group corresponding to R1xe2x80x2 or R2xe2x80x2, as described in J. Am. Chem. Soc., 87, 1353 (1956).
An optical active compound represented by the general formula (XII) can be produced by reducing the compound represented by the general formula (II) or a substituted mandelic acid derivative in which the xcex1-carbon atom (*1) is in a desired absolute configuration into a corresponding glycol derivative, tosylating or mesylating or halogenating, then, the resulting primary alcohol and cyclizing the resulting compound using a strong base, such as an alkali metal hydroxide, under a usual intramolecular nucleophilic substitution reaction.
 less than  less than Production Process C greater than  greater than 
Alternatively further, there is a method for producing a racemic modification by condensing a phenylglyoxal compound represented by the general formula (XIII) 
in which R1xe2x80x2 and R2xe2x80x2 have the same meanings as those given previously with an amine compound represented by the general formula (III) in which Y is hydrogen atom and X, R6, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2 and *2 have the same meanings as those given previously and reducing the resulting compound, with final deprotection of the protecting groups A, Axe2x80x3, Axe2x80x3xe2x80x2, the protecting group for the amino group of R3xe2x80x2 and the protecting acetyl group of R1xe2x80x2 by the procedure described in the paragraph of xe2x80x9cProduction Process Axe2x80x9d, with the proviso that the deprotection of the protecting group A is unnecessary when R1 is benzyloxy and the protecting group A is benzyl.
This reaction is carried out in general in a reaction solvent by reducing the Schiff base resulting from the condensation reaction using an adequate reducing agent capable of reducing the Schiff base and at the same time reducing the oxo-group into hydroxyl group. As the reducing agent, there may be employed, for example, sodium borohydride, sodium cyanoborohydride and lithium cyanoborohydride. The proportion of the phenylglyoxal compound to the amine compound is in general 1-3 moles, preferably 1-1.5 moles of the former to 1 mole of the amine compound. Reaction may be carried out at an adequate temperature and, in general, at a temperature from room temperature to the reflux temperature of the solvent employed. The reaction duration may adequately be chosen in accordance with the reaction condition and so on and may be terminated at a point at which the reaction yield becomes highest. The above reactions may be carried out in a reaction solvent based on alcohol, such as methanol or ethanol, preferably at a low temperature in the presence of sodium borohydride.
The compound of the general formula (XIII) can be obtained easily by oxidizing an acetophenone derivative substituted by R1xe2x80x2 and R2xe2x80x2 in a reaction medium of water or an organic solvent, for example, acyclic ether, such as dioxane or tetrahydrofuran, using an oxidizing agent, such as selenium dioxide. Alternatively, it can be produced by the process described in J. Am. Chem. Soc. 79, 6562 (1957).
 less than  less than Production Process D greater than  greater than 
The compound represented by the general formula (I) in which R is hydrogen atom and R1, R2, R6, X, R7, R8, R9, *1 and *2 have the same meanings as those given previously can be obtained also by reacting an amine compound represented by the general formula (XIV), 
in which R1xe2x80x2, R2xe2x80x2 and *1 have the same meanings as those given previously, with a compound represented by the general formula (XV), 
in which R6, X, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2 and *2 have the same meanings as those given previously and Z denotes an eliminable group, followed by deprotection of the protecting groups A, Axe2x80x3, Axe2x80x3xe2x80x2, that protecting the amino group in R3xe2x80x2 and the protecting acetyl group in R1xe2x80x2 by the method described in the paragraph xe2x80x9cProduction Process Axe2x80x9d, with the proviso that the deprotection of the protecting group A is unnecessary when R1 is benzyloxy and the protecting group A is benzyl.
By effecting the coupling reaction with the amine compound in an organic solvent, if necessary, in the presence of a proton-acceptor, such as a tertiaryamine, for example, triethylamine, the compound represented by the general formula (I) is obtained. The xe2x80x9celiminable groupxe2x80x9d means a group which is eliminated upon the above reaction of the chloride, bromide or iodide group or mesyl or tosyl group with, for example, sulfonate or so on. The reaction may be realized, for example, using, in general, 1-10 moles of the amine compound represented by the general formula (XIV) per one mole of the compound represented by the general formula (XV).
Since this reaction proceeds at a lower velocity, the reaction may preferably be effected in an autoclave in a reaction solvent, for example, an alcohol, such as methanol, ethanol or butanol, a halogenated hydrocarbon, such as methylene chloride or chloroform, or tetrahydrofuran or dioxane. The reaction temperature is chosen, in general, in the range from 10 to 150xc2x0 C. preferably from 70 to 130xc2x0 C. The reaction duration is chosen, in general, in the range from 5 to 100 hours.
The compound of the general formula (XIV) can be obtained by hydrogenating a substituted mandelonitrile substituted by R1xe2x80x2 and R2xe2x80x2 in the presence of a catalyst, such as Raney nickel. The substituted mandelonitrile can be produced by a reaction of a substituted benzaldehyde with hydrogen cyanide or with sodium cyanate together with sodium hydrogen sulfite as a racemic compound from which each optical active isomer can easily be separated by methods and techniques employed commonly by preparing salts of the diastereomers with an optically active acid selected adequately. The optically active substituted mandelonitrile derivative can be obtained by reacting the optically active carboxylic acid resulting from hydrolysis of the optically active substituted mandelonitrile with ammonia in the presence of a commonly employed condensing agent, followed by reduction of the resulting product.
The compound of the general formula (XV) can be obtained by reacting a phenol compound represented by the general formula (VIII) with a compound represented by the general formula (XVI), 
in which R6 and *2 have the same meanings as those given previously and Bxe2x80x2 is a halogen atom, or with a compound represented by the general formula (XVII), 
in which R6 and *2 have the same meanings as those given previously, under the condition of synthesizing the compound represented by the general formula (III) described in the paragraph of xe2x80x9cProduction Process Axe2x80x9d, followed by tosylating or mesylating the alcohol resulting from the above reaction with the compound represented by the general formula (XVI).
 less than  less than Production Process E greater than  greater than 
The compound represented by the general formula (I) in which R is methyl can be produced by methylating the alcohol compound of the general formula (I) in which R is hydrogen atom produced by the xe2x80x9cProduction Processxe2x80x9d A, B, C or D under a commonly employed acidic condition. Thus, the compound of the general formula (I) in which R is methyl can be produce by treating the compound of the general formula (I) in which R is hydrogen atom with hydrogen chloride in methanol at a temperature from room temperature to the boiling point of the reaction medium.
The compound represented by the general formula (XVIII), 
in which R1xe2x80x2, R2xe2x80x2, R6, Y , X, R7xe2x80x2, R8xe2x80x2, R9xe2x80x2, *1 and *2 have the same meanings as those given previously, which is a compound in which the amino group of the amine compound formed in the process for producing the compound represented by the general formula (I) in which R is hydrogen atom is protected by the protecting group Yxe2x80x2 and in which a possible protecting group Axe2x80x2 for the hydroxyl group, if present, is de-protected by the method described above, is processed by methylation of the hydroxyl group by a commonly used technique. By de-protecting the protecting group Yxe2x80x2 for the amino group and those of A, Axe2x80x3, Axe2x80x3xe2x80x2 and that protecting the amino group in R3xe2x80x2, if present, as well as the protecting acetyl group in R1xe2x80x2, with the proviso that the deprotection of the protecting group A is unnecessary when R1 is benzyloxy and the protecting group A is benzyl, the compound represented by the general formula (I) in which R is methyl and R1, R2, R6, X, R7, R8, R9, *1 and *2 have the same meanings as those given previously is obtained.
A concrete example of methylation of the hydroxyl group consists in that the compound is reacted with 1-5 equivalents of methyl iodide or methyl bromide in the presence of a base, such as potassium carbonate, triethylamine, sodium hydroxide or sodium hydride, in a solvent, such as dimethylsulfoxide, dimethylformamide, dimethoxyethane or tetrahydrofuran, at a temperature in the range from room temperature to the reflux temperature of the solvent. An alternative embodiment consists in that the compound is reacted, in a form of its alkaline solution containing sodium hydroxide or potassium hydroxide in water or in methanol, with 2-10 equivalents of dimethyl sulfate at a temperature in the range from room temperature to the reflux temperature of the solvent.
The starting compounds of the present invention may, if necessary, be purified, wherein known chromatographic techniques including column-, flush column-, thin layer- and high performance liquid chromatography may be employed therefor by taking into account of such a parameter as the Rf value given in this specification.
As described above, the compound represented by the general formula (I) may be present as four or two different isomers. The process according to the present invention can provide both the pure isomer and the racemic mixture. The reactions described above do not alter the pertaining stereo chemistry.
Therefore, starting from the compound of the general formula (V) or of the general formula (XIII) having no asymmetric carbon atom, starting from the racemic compound represented by the general formula (II), (XII) or (XIV), or starting from the racemic compound represented by the general formula (III) or (XV), isomeric mixtures (R,R), (R,S), (S,S) and (S,R) are obtained. Similarly, starting from the pure isomer of the general formula (III) or (XV) and, for example, from the R-isomer of the general formula (III), mixtures of only two isomers (R,R) and (S,R) are obtained and, if an optical active isomer of the general formula (II), (XII) or (XIV) is employed, corresponding pure isomer can be obtained.
When a mixture of the four isomers or of two isomers is obtained, the isomers can be separated by a pertinent technique, such as fractional crystallization or the like, as their addition salts with an optically active acid, such as camphor sulfonic acid, mandelic acid or a substituted mandelic acid. The fractional crystallization may be performed using an adequate solvent, preferably a lower alkanol, such as ethanol or isopropanol or a mixture of them.
Every pair of the enantiomers can be separated into each optical active isomer by, for example, forming a diastereomeric salt and chromatographic separation on an optically active column, or by other means. When one of the starting raw materials is optically active, the mixture of the diastereomers obtained as above can be divided into each pure isomer. By separating each of the optical active isomers and purifying it, it becomes possible to improve the pharmacological effect or to eliminate side effects by using only the isomer having more higher activity which is preferable as a medicament.
As the salt of the compound represented by the general formula (I) according to the present invention, there may be exemplified salts with known acids, for example, addition salts thereof with mineral acids and organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen sulfuric acid, dihydrogen phosphoric acid, citric acid, maleic acid, tartaric acid, fumaric acid, gluconic acid and methane sulfonic acid: and with optically active acids, such as camphor sulfonic acid, mandelic acid and substituted mandelic acids, wherein special preference is given to those which are medicamentally acceptable.
For preparing a salt of the compound represented by the general formula (I), the compound of the general formula (I) is dissolved in an alcohol, such as methanol or ethanol, and the acid component is added to the resulting alcoholic solution, whereby the corresponding acid addition salt can be obtained. Examples of the acids to be used therefor include mineral acids and organic acids which are medicamentally acceptable, such as hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen sulfuric acid, dihydrogen phosphoric acid, citric acid, maleic acid, tartaric acid, fumaric acid, gluconic acid and methane sulfonic acid.
The tricyclic compounds and the pharmacologically acceptable salts according to the present invention have no recognizable toxicity and are useful as medicaments and exhibit, for example, xcex23-activity, so that they can be utilized as medicaments for therapeutic and preventive treatments of xcex23-correlating diseases. The xe2x80x9cxcex23-correlating diseasesxe2x80x9d is a generic expression for diseases which can be improved by a functional activity mediated xcex23-adrenaline receptor and include, for example, diabetes, obesity, hyperlipemia. diseasses in digestive system, such as abnormal motion and ulcer in digestive system, and depression. In particular, the compound according to the present invention serves for treating diabetes, obesity and hyperlipemia. Thus, the compound according to the present invention is effective as a medicament for preventive or therapeutic treatment of diabetes due to its function for decreasing the blood sugar value and is also effective for preventive treatment of hyperlipemia and therapeutic treatment of obesity due to its lipolytic activity.
In preparing a medicament from the compound according to the present invention, it is preferable to admix, if necessary, to an effective amount of the tricyclic compound represented by the general formula (I) or salt thereof a pharmacologically acceptable carrier to formulate a drug composition. As the pharmacologically acceptable carrier, there may be exemplified excipients, binding agents, such as carboxymethylcellulose etc., disintegrator, lubricants and various additives.
For administering the drug containing the compound according to the present invention to human, oral administration of the drug in a form of tablet, powder, granules, capsule, sugar-coated tablet, liquid drug or syrup. Drugs for parenteral administration, such as injection drugs, may also be possible. The dose amount of administration may be different in accordance with the age, body weight, significance of the disease, symptom and so on and the dose may, in general, be in an amount of 0.01-2.000 mg per day for an adult all at once or allotted in several administrations. The term for receiving such drug may in general, range from several weeks to several months with daily administration, while it is possible to increase or decrease both the term and the daily dose in accordance with the state of the disease of patient.